title: N-cadherin-mediated cell adhesion restricts cell proliferation in the dorsal neural tube.
abstract: Neural progenitors are organized as a pseudostratified epithelium held together by adherens junctions (AJs), multiprotein complexes composed of cadherins and α- and β-catenin. Catenins are known to control neural progenitor division; however, it is not known whether they function in this capacity as cadherin binding partners, as there is little evidence that cadherins themselves regulate neural proliferation. We show here that zebrafish N-cadherin (N-cad) restricts cell proliferation in the dorsal region of the neural tube by regulating cell-cycle length. We further reveal that N-cad couples cell-cycle exit and differentiation, as a fraction of neurons are mitotic in N-cad mutants. Enhanced proliferation in N-cad mutants is mediated by ligand-independent activation of Hedgehog (Hh) signaling, possibly caused by defective ciliogenesis. Furthermore, depletion of Hh signaling results in the loss of junctional markers. We therefore propose that N-cad restricts the response of dorsal neural progenitors to Hh and that Hh signaling limits the range of its own activity by promoting AJ assembly. Taken together, these observations emphasize a key role for N-cad-mediated adhesion in controlling neural progenitor proliferation. In addition, these findings are the first to demonstrate a requirement for cadherins in synchronizing cell-cycle exit and differentiation and a reciprocal interaction between AJs and Hh signaling.
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, USA.
authors.forename: Kavita
authors.initials: K
authors.lastname: Chalasani
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Brewster
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002923:Cilia / Q000473:pathology; D053823:Hedgehog Proteins / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D054259:Neural Tube / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D015820:Cadherins; D053823:Hedgehog Proteins; C513786:N-cadherin, zebrafish; D029961:Zebrafish Proteins